It is frequently desirable to coat oral pharmaceutical tablet cores with an enteric coating. An enteric coating resists dissolution in acidic gastric media, but dissolves in the alkaline intestinal environment. Enteric coatings are useful for protecting the stomach wall from the effect of active ingredients in dosage form. For example, if aspirin is directly exposed to gastric mucosa, it can cause corrosion of the stomach wall. Enteric coatings are also used to protect active ingredients in the tablet core from chemical attack from stomach acids and digestive enzymes. Enteric coatings can also be used to promote the delivery of active ingredients in the core tablet to a particular region of the intestine such as the upper part of the small intestine, in order to enhance the bioavailability of the active ingredient.
Polymers useful as enteric coatings contain ionizable carboxylic groups and include cellulose acetate phthalates(C-A-P), cellulose acetate trimellitates(C-A-T), hydroxypropyl methyl cellulose phthalates(HPMCP), hydroxypropyl methyl cellulose acetate succinate (HPMCAS), polyvinyl acetate phthalate (PVAP), and certain acrylic polymers. In the low pH stomach environment, the carboxylic acid groups in the polymers remain un-ionized. Therefore, the polymeric coating remains insoluble in gastric fluid. The polymeric coating disintegrates or dissolves in the higher pH intestinal environment to allow dissolution of the tablet core in the small intestine. The active ingredients are absorbed through the intestinal wall for delivery to the blood stream.
Originally these polymers were applied to tablets as solutions in various organic solvents since the polymers are soluble in organic solvents. The use of organic solvents, however, is objectionable from environmental, physiological, and safety standpoints, as well as for economic reasons.
The use of organic solvents has been avoided by applying the polymers as aqueous solutions or dispersions of their water-soluble salts. The enteric polymers are water-solubilized with a water soluble base through neutralization of a sufficient number of carboxyl groups so that the polymer becomes water soluble or water dispersible. Useful water soluble bases include alkali metal hydroxides and ammonium hydroxide. The water soluble salts of enteric cellulose esters have been found to be somewhat hydrolytically unstable, hydrolyzing slowly upon exposure to atmospheric moisture or gastric juices. A resulting film of partly hydrolyzed polymer is partially insoluble in intestinal fluid, causing the active ingredient to be released too slowly in the intestinal tract.
Parker et al, J. Pharm. Sci. 63, 119-215(1974); Okhamafe & York, Int. J. Pharm. 22 (2-3) (1984), and Okhamafe & York (1984)disclose that the presence of solid filler material in film dispersed from a solution of a water soluble salt of an enteric polymer reduces polymer film hydrolysis.
Parker, et al disclose that the reduction in film hydrolysis is directly related to film thickness. However, a thicker film takes longer to disintegrate in the intestine. Similarly, Porter, Pharm. Tech., March, 1980, pp 67-75, discloses that while low loadings of solid pigment material can somewhat increase film resistance to moisture, higher filler loading levels which would add more water resistance detrimentally affect the mechanical strength of the film. High tensile strength is required for a useful tablet coating. Therefore, the amount of solid filler material used for increasing water resistance is limited by decreased mechanical strength.
In light of the above, it would be desirable to provide an aqueous enteric coating composition containing a water soluble salt of a film-forming enteric polymer wherein the film coating provides a higher water resistance than was previously achievable and maintains good mechanical strength.